Positron emission tomography (PET) is a precise and non-invasive medical imaging technique. In practice, a radiopharmaceutical molecule labelled by a positron-emitting radioisotope, in situ disintegration of which results in the emission of gamma rays, is injected into the organism of a patient. These gamma rays are detected and analysed by an imaging device in order to reconstruct in three dimensions the biodistribution of the injected radioisotope and to obtain its tissue concentration.
Fluorine 18 (T1/2=109.6 min) is the only one of the four light positron-emitting radioisotopes of interest (11C, 13N, 15O, 18F) that has a half-life long enough to allow use outside its site of production.
Among the many radiopharmaceuticals synthesised from the radioisotope of interest, namely fluorine 18, 2-[18F]fluoro-2-deoxy-D-glucose (FDG) is the radio-tracer used most often in positron-emission tomography. In addition to the morphology imaging, PET performed with 18F-FDG allows to determine the glucose metabolism of tumours (oncology), myocardium (cardiology) and brain (psychology).
The 18F radioisotope in its anionic form (18F−) is produced by bombarding a target material, which in the present case consists of 18O-enriched water (H218O), with a beam of charged particles, more particularly protons.
To produce said radioisotope, it is common practice to use a device constituting an irradiation cell comprising a cavity “hollowed out” in a metal part and intended to house the target material used as precursor. This metal part is usually called an insert.
The cavity in which the target material is placed is sealed by a window, called “irradiation window” which is transparent to the particles of the irradiation beam. Through the interaction of said particles with the said target material, a nuclear reaction occurs which leads to the production of the radioisotope of interest.
The beam of particles is advantageously accelerated by an accelerator such as a cyclotron.
Because of an ever increasing demand for radioisotopes, and in particular for the 18F radioisotope, efforts are made to increase the yield of the above mentioned nuclear reaction. This is done either by modifying the energy of the beam of particles (protons), making use of the dependence of thick target yield on the particle energy, or by modifying the intensity of the beam, thereby modifying the number of accelerated particles striking the target material.
However, the power dissipated by the target material irradiated by the accelerated particle beam limits the intensity and/or the energy of the particle beam that is being used. This is because the power dissipated by a target material is determined by the energy and the intensity of the particle beam through the following equation:P (watts)=E (MeV)×I(μA)where:                P=power expressed in watts;        E=energy of the beam expressed in MeV; and        I=intensity of the beam expressed in μA.        
In other words, the higher the intensity and/or the energy of the particle beam, the higher will be the power to be dissipated by a target material.
It will consequently be understood that the energy and/or the intensity of the beam of accelerated charged particles cannot be increased without rapidly generating, within the cavity of the production device, and at the irradiation window, excessive pressures or temperatures liable to damage said window.
Moreover, in the case of 18F radioisotope production, given the particularly high cost of 18O-enriched water, only a small volume of this target material, used as a precursor material, at the very most a few milliliters, is placed in the cavity. Thus, the problem of dissipating the heat produced by the irradiation of the target material over such a small volume constitutes a major problem to be overcome. Typically, the power to be dissipated for a 18 MeV proton beam with an intensity of 50 to 150 μA is between 900 W and 2700 W, and this in a volume of 18O-enriched water of 0.2 to 5 ml, and for irradiation times possibly ranging from a few minutes to a few hours.
More generally, given this problem of heat dissipation by the target material, the irradiation intensities for producing radioisotopes are currently limited to 40 μA for an irradiated target material volume of 2 ml in a silver insert. Current cyclotrons used in nuclear medicine are however theoretically capable of accelerating proton beams with intensities ranging from 80 to 100 μA, or even higher. The possibilities afforded by current cyclotrons are therefore under-exploited.
Solutions have been proposed in the prior art for overcoming the problem of heat dissipation by the target material in the cavity within the radioisotope production device. In particular, it has been proposed to provide means for cooling the target material.
Accordingly, document BE-A-1011263 discloses an irradiation cell comprising an insert made of Ag or Ti, said insert comprising a hollowed-out cavity sealed by a window, in which cavity the target material is placed. The insert is placed in co-operation with a ‘diffusor’ element which surrounds the outer wall of said cavity so as to form a double-walled jacket allowing the circulation of a refrigerant for cooling said target material. For improving heat flow out of the cavity, a cavity having a wall as thin as possible is desirable. However, when silver is used as material for the cavity, wall porosity becomes a problem when wall thickness is smaller than 1.5 mm.
The materials for manufacturing the device according to the present invention have to be selected in a cautious way. In particular, the choice of the insert material is particularly important. It is indeed necessary to avoid the production of undesirable by-products during irradiation which would lead to a remaining activity. By way of example, it is necessary to avoid the production of such radioisotopes that disintegrate by high-energy gamma particle emission and make any mechanical intervention on the target difficult due to radiosafety problems. Indeed, the overall activity of the insert measured after irradiation and total emptying of said insert has to be as low as possible. Titanium is chemically inert but under proton irradiation produces 48V having a half-life of 16 days. Consequently, in the case of titanium, should a target window break, its replacement would pose serious problems for the maintenance engineers who would be exposed to the ionizing radiation.
In addition, when choosing the type of material for the inserts of the device according to the invention, another key parameter is its thermal conductivity. Thus, silver is a good conductor but does have the drawback that, after several irradiation operations, it forms silver compounds that can block the emptying system.
It would be ideal to use niobium for the insert, this material having a thermal conductivity two and a half times higher than titanium (53.7 W/m/K for Nb and 21.9 W/m/K for Ti), though eight times lower than silver (429 W/m/K). Niobium is chemically inert and produces few isotopes of long half-life. Therefore, niobium is a good compromise. However, niobium is a difficult material to use in an insert of complex design, as it is difficult to machine. A built-up edge may occur on the tools, leading to high tool wear. Eventually, the tool may break. The use of electrical discharge machining is not a solution either: the electrodes wear out without shaping the piece to be machined. In particular, the insert described in document BE-A-1011263 is of a complex structure, which would be difficult to produce in niobium.
Also, using prior art insert forms and materials, it is impossible to produce a more elongated insert, which would be beneficial as it would provide a larger surface for the thermal exchange.
Tantalum is also a material having interesting properties, but, which is, like niobium, difficult to machine. Tantalum has a thermal conductivity (57.5 W/m/K) slightly higher (better) than Niobium.
Document WO02101757 is related to an apparatus for producing 18F-Fluoride, wherein an elongated chamber is present, for containing the gaseous or liquid target material which is to be irradiated. The chamber can be made from niobium. However, this apparatus does not comprise what is defined as an ‘insert’, a separate part comprising the cavity, which is to be introduced in the irradiation cell. The apparatus of WO02101757 comprises several parts assembled together, but there is no distinction between the cell and the insert. The same is true for the irradiation devices described in U.S. Pat. No. 5,917,874, US2001/0040223 and U.S. Pat. No. 5,425,063.